Korean drugmakers are moving into next-generation cancer therapies targeting POLQ, or polymerase theta, a DNA repair protein described as cancer cells' last lifeline. With Daewoong Pharmaceutical (069620) already developing a POLQ inhibitor, a separate patent on a new compound has now been confirmed at Dong-A ST, raising the question of whether competition will intensify over next-generation synthetic lethality drugs designed to move beyond the limits of existing PARP inhibitors, which block DNA repair.
Dong-A ST published an international patent in January covering a new compound that inhibits POLQ, according to pharmaceutical industry sources on the 26th. No specific target cancer types or clinical development plans have been disclosed, but POLQ is drawing attention as a next-generation synthetic lethality target that can selectively attack cancer cells with weakened DNA repair capacity, such as those with BRCA1 and BRCA2 mutations or homologous recombination deficiency (HRD).
BRCA1 and BRCA2 are genes responsible for properly repairing damaged DNA. Cancer cells with defects in these genes have reduced DNA repair capacity, and when PARP, another repair protein, is also blocked with a drug, DNA damage accumulates and the cancer cells die. This is the principle known as synthetic lethality, which exploits a specific genetic defect in cancer cells to kill them selectively.
PARP inhibitors have already established themselves in the global cancer drug market. Lynparza (olaparib), developed by AstraZeneca and MSD, started in ovarian cancer and expanded into BRCA-mutated breast cancer, pancreatic cancer and prostate cancer. GSK's Zejula (niraparib) is used to treat ovarian cancer, and Pfizer's Talzenna (talazoparib) is used for BRCA-mutated HER2-negative breast cancer and certain metastatic castration-resistant prostate cancers.
The market is also growing quickly. The global DNA damage repair (DDR) therapy market, which includes PARP and POLQ inhibitors, is expected to nearly double to $11.2 billion in 2030 from $5.8 billion in 2024, according to market research firm Strategic Market Research. That translates into an average annual growth rate of 11.4%. No POLQ inhibitor has been commercialized yet, so no separate market has formed, but that outlook explains the continuing race to claim the next-generation DDR target that will follow PARP inhibitors.
PARP inhibitors have limits, however. As treatment continues, some cancer cells can acquire resistance by using other DNA repair pathways. That is what has pushed POLQ forward as a new target. POLQ serves as a kind of emergency DNA repair mechanism that cancer cells with impaired normal DNA repair capacity rely on to survive.
In Korea, Daewoong Pharmaceutical is running preclinical development of DWP223, a POLQ inhibitor. DWP223 was selected as a project by the Korea Drug Development Fund and is being developed from 2025 to 2027 as a synthetic lethality cancer drug for patients with BRCA-mutated solid tumors. With Daewoong Pharmaceutical having disclosed its POLQ drug development and Dong-A ST's own patent on a new compound now confirmed, competition among Korean drugmakers to claim next-generation DNA repair targets in oncology is becoming visible.
Global rivals are a step ahead in clinical development. ART6043, a POLQ inhibitor from Britain's Artios, has been studied in early trials as a monotherapy and in combination with the PARP inhibitor olaparib across various advanced and metastatic solid tumors. A trial is currently underway comparing ART6043 plus olaparib with olaparib alone in patients with germline BRCA-mutated HER2-negative advanced or metastatic breast cancer.
"POLQ is significant in that it can target tumors with genetic characteristics such as BRCA mutations or HRD, rather than specific cancer types themselves," an industry expert said. "If combination use with PARP inhibitors or the potential to overcome resistance is confirmed in clinical trials, its value as a next-generation cancer target could rise further."
